Cytochrome C Oxidase Assembly Factor 1 Homolog Predicts Poor Prognosis and Promotes Cell Proliferation in Colorectal Cancer by Regulating PI3K/AKT Signaling

Abstract

Yuan Xue,1,2,* Pei-Dong Li,1,2,* Xue-Mei Tang,3,* Zai-Hua Yan,1,2 Shu-Sen Xia,1 Hong-Peng Tian,1 Zuo-Liang Liu,1 Tong Zhou,1 Xue-Gui Tang,4 Guang-Jun Zhang1,2 1The Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 2Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 3Department of Ultrasound, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 4Anorectal Department of Integrated Traditional Chinese and Western Medicine, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xue-Gui TangAnorectal Department of Integrated Traditional Chinese and Western Medicine, The Affiliated Hospital of North Sichuan Medical College, 63 Wenhua Road, Nanchong 637000, Sichuan, People’s Republic of ChinaTel [phone]Email [email protected] ZhangThe Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, 63 Wenhua Road, Nanchong 637000, Sichuan, People’s Republic of ChinaTel [phone]Email [email protected]: Colorectal cancer (CRC) is one of the most common malignancies in the world. The prognosis of advanced CRC is still poor. The purpose of this study was to identify a gene expression profile associated with CRC that may contribute to the early diagnosis of CRC and improve patient prognosis.Patients and Methods: Five pairs of CRC tissues and paracancerous tissues were used to identify causative genes using microarray assays. The prognostic value of Cytochrome C Oxidase Assembly Factor 1 Homolog (COA1) in CRC was assessed in 90 CRC patients. Loss-of-function assays, cell proliferation assays using Celigo and MTT, colony formation assays, a subcutaneous xenograft mouse model, and apoptosis assays were used to define the effects of downregulation of COA1 in CRC cells in vitro and in vivo. The underlying molecular mechanisms of COA1 in CRC were also investigated.Results: The causative gene COA1 was identified through microarray analysis. COA1 expression in CRC was notably associated with pathologic differentiation, tumor size, and tumor depth. COA1 expression may act as an independent prognostic factor for overall survival of CRC. Knockdown of COA1 inhibited the proliferation of CRC cells in vitro and the tumorigenicity of CRC cells in vivo. Decreased COA1 expression induced apoptosis of CRC cells. Based on the microarray assay results comparing HCT116 cells transfected with lentivirus encoding anti-COA1 shRNA or negative control shRNA, ingenuity pathway analysis (IPA) revealed that the PI3K/AKT signaling pathway was significantly enriched. Moreover, CCND1, mTOR, AKT1, and MDM2 were identified as the downstream genes of COA1.Conclusion: These findings demonstrate that COA1 promotes CRC cell proliferation and inhibits apoptosis by regulating the PI3K/AKT signaling pathway. Our results implicate COA1 as a potential oncogene involved in tumor growth and progression of CRC.Keywords: colorectal cancer, COA1, proliferation, apoptosis, PI3K/AKT signaling

Keywords

• colorectal cancer
• coa1
• proliferation
• apoptosis
• pi3k/akt signaling